See http://www.cafc.uscourts.gov/images/stories/opinions-orders/10-1513.pdf
Issue(s): Was the lower court correct in granting a summary judgment invalidating the two claims of U.S. Patent No. 5,211,954 (“the ’954 patent”) for obviousness?
TYCO HEALTHCARE GROUP LP AND MALLINCKRODT, INC., Plaintiffs Appellants, v. MUTUAL PHARMACEUTICAL COMPANY, INC. AND UNITED RESEARCH LABORATORIES, INC., Defendants-Appellees, 2010-1513, Appeal from the United States District Court for the District of New Jersey in Case No. 07-CV-1299, Judge Stanley R. Chesler. (Decided: June 22, 2011); Before NEWMAN, BRYSON(Author), and GAJARSA,
Facts: Temazepam is a hypnotic (sleep-inducing) drug that is one of a class of compounds known as benzodiazepines. Pharmacological formulations of temazepam have been marketed internationally for the treatment of insomnia since the 1970s, and in the United States since 1981 under the name Restoril®. Tyco holds the rights to the ’954 patent, which has two claims for temazepam formulations. Claim 1 reads: A hard gelatin capsule containing a temazepam formulation consisting essentially of 6 to 8 milligrams of crystalline temazepam having a surface area of from 0.65 to 1.1 m2/g and 95% of the temazepam having a particle size of less than 65 microns in admixture with a pharmaceutically acceptable carrier therefor.
Lower Court’s Decision: In November 2006, Mutual Pharmaceutical Company, Inc., filed an Abbreviated New Drug Application (“ANDA”) with the U.S. Food and Drug Administration (“FDA”) seeking approval to manufacture and sell a generic version of 7.5 mg temazepam capsules. Tyco responded in March 2007 by filing an infringement action against Mutual and United Research Laboratories, Inc. (collectively, “Mutual”). In July 2009, after Mutual had received tentative FDA approval of its ANDA, Tyco moved for a preliminarily injunction to prevent Mutual from selling its generic temazepam capsule. The district court denied Tyco’s motion based on uncontroverted evidence that Mutual’s ANDA disclosed a product that could not literally infringe the ’954 patent because the ANDA required the surface area of the crystalline temazepam to be at least 2.2 square meters per gram.
Mutual then moved for summary judgment of non-infringement and invalidity. The district court granted Mutual’s motion with respect to invalidity, concluding that Mutual had shown by clear and convincing evidence that the ’954 claims were obvious and that no reasonable trier of fact could find to the contrary. In reaching that conclusion, the court noted, first, that Restoril® capsules had been sold in the United States in 15 mg and 30 mg dosages more than a year before the priority date of the ’954 patent. Second, the court looked to a 1983 volume of the British National Formulary (“BNF”), a medical reference book published in the United Kingdom, which directed physicians to the use of temazepam at a dosage between 5 and 15 mg for the treatment of insomnia in the elderly. Third, the court observed that the parties did not dispute that “physicians always seek to prescribe the lowest effective dose of any medication, particularly hypnotics such as temazepam.” Based on those undisputed facts, the court concluded that it would have been obvious to a person of ordinary skill in the art to combine the preexisting 15 mg Restoril® capsule with the dosage range identified in the BNF reference. Tyco appeals the district court’s order invalidating the ’954 claims.
Findings on Appeal: the only limitation of the two ’954 claims that was not fully disclosed by the prior art Restoril® capsules is the lower dosage of temazepam. Ordinarily, “where there is a range disclosed in the prior art, and the claimed invention falls within that range, there is a presumption of obviousness.” That presumption is rebuttable either by a showing that the prior art taught away from the invention or by a showing of new and unexpected results relative to the prior art. Tyco argues first that the BNF reference does not direct a person of ordinary skill in the art to temazepam hard capsules in the 5 to 15 mg dosage range. It then argues that the prior art as a whole taught away from a range of 6 to 8 mg. Finally, Tyco contends that secondary considerations of new and unexpected results and commercial success support a finding of non-obviousness.
Tyco contests the district court’s interpretation of the BNF reference. The BNF is a medical reference book published semi-annually by the British Medical Association and the Pharmaceutical Society of Great Britain. The Preface to the BNF explains that it serves as “a pocket book for rapid reference . . . for prescribing and dispensing” drugs. In regard to temazepan, the reference states: Dose: 10-30 mg (elderly patients 5-15 mg), increasing in severe insomnia to 60 mg, 30 minutes before bedtime The district court concluded that “[t]his entry plainly tells one of skill in the art to treat insomnia in the elderly by administering a dose in the range of 5 to 15 mg.
Tyco contests the district court’s interpretation of the BNF reference. It relies on the declaration of its expert, Dr. William Orr, who stated that “[a] person of ordinary skill in the art would not interpret [the BNF] reference as recommending any particular dose.” The district court, however, concluded that Dr. Orr had not offered a factual basis for his conclusion or explained his rationale and therefore discredited his characterization of the BNF. Dr. Orr’s statements did not contest the fact that the BNF refers to dosages of temazepam between 5 and 15 mg. His statements are directed to the utility of temazepam as a treatment for insomnia.
Tyco argues that all the properties of a composition of matter relevant to patentability must be considered in evaluating whether that composition would have been obvious in light of the prior art, and that the unclaimed property of effectiveness in treating insomnia renders the claims at issue nonobvious. That argument is unavailing. “The discovery of a new property or use of a previously known composition, even when that property and use are unobvious from the prior art, can not impart patentability to the known composition.”
Tyco does not dispute that, at the time the BNF was published, 5 mg temazepam hard capsules had been sold abroad for more than a decade under the name Levanxol®. In addition, the record contains two prior art publications discussing experimentation with 5 mg capsules: a 1970 Italian study (“Senini”) and a 1974 Indian study (“Sardesai”).
First, as already discussed, the ’954 claims are not tied to product efficacy, so the absence of any particularized discussion of efficacy in the BNF reference is immaterial to obviousness of the composition here claimed in light of the prior art showing general efficacy for the same use. Second, none of the specialized publications cited by Dr. Orr and Tyco undermine the teaching of the BNF reference that a person of ordinary skill in the art could consider temazepam dosages between 5 mg and 15 mg to treat insomnia.
Two of the specialized publications cited by Tyco are articles from the 1970s by the same authors (“Nicholson 1976” and “Nicholson 1979”). The first reference, Nicholson 1976, described a sleep study conducted with six males between the ages of 19 and 43. The experimenters administered 10 mg and 20 mg doses of temazepam to the subjects. The experiment disclosed that 10 mg temazepam doses produced a “marked reduction in sleep onset latency”—i.e., the time it takes a person to fall asleep—but resulted in “little or no increase in total sleep time.”
Tyco argues that Nicholson 1976 taught that 10 mg capsules were “ineffective because they do not affect the ‘key’ requirement of total sleep time.” According to Tyco, “effectiveness as a sleeping pill requires both that sleep latency is decreased and total sleep time is increased.” Tyco cites the ’954 patent, Dr. Orr’s declaration, and a 1983 publication (“Matejcek”) in support of that proposition. Tyco also points out that Nicholson 1976 taught that 20 mg temazepam capsules are effective for treatment of insomnia. The study found a statistically significant increase in total sleep time and decrease in sleep onset latency following administration of 20 mg temazepam capsules. However, that result is not pertinent to the issue in this case because it does not teach away from the efficacy of 7.5 mg capsules.
The second reference, Nicholson 1979, described a sleep study conducted with six middle-aged males between the ages of 45 and 55. The experimenters administered 10, 20, and 30 mg doses of temazepam. The experimental results revealed no statistically significant change in total sleep time or sleep onset latency after administration of any of those dosages of temazepam. Tyco argues that “Matejcek would have directly discouraged [a person of ordinary skill in the art] from the idea that hard capsules with 7.5 mg of temazepam would be effective to treat insomnia.”
There are two problems with Tyco’s argument. First, the Matejcek study did not identify whether hard or soft capsules were used in its experiment. The prosecuting attorney for the ’954 patent represented to the PTO that Matejcek “clearly state[s]” that the capsules used were soft capsules, but there is no support for that statement in the record. After Mutual pointed out the lack of evidence on that point in its brief, Tyco refrained from characterizing the Matejcek capsule as a soft capsule in its reply brief.
Second, the only prior art reference in the record before this court that could conceivably have given rise to Tyco’s alleged 1:1.5 efficacy ratio is a published article from 1977 (“Fuccella 1977”). That reference disclosed an experiment on six males between the ages of 21 and 33 using both soft and hard capsules of temazepam.
Essentially, Tyco’s argument is based on a passing mention in an article of a subjective sleep evaluation study described in another article in which 20 mg soft capsules performed better than 30 mg hard capsules. However, Tyco did not refer to either of those articles as relevant prior art in its opening brief. Moreover, according to Tyco’s own argument that measurement of several objective sleep parameters (e.g., sleep onset latency and total sleep time) is required to evaluate the efficacy of a sleeping pill, the subjective sleep evaluation study that could ultimately have led to Tyco’s 1:1.5 ratio would not have been able to measure sleeping pill efficacy with accuracy. Nor did the Matejcek study measure those parameters. In sum, Tyco’s argument that the Matejcek reference teaches away from use of a 7.5 mg hard capsule of temazepam to treat insomnia is not supported by evidence in the record.
Tyco argues that secondary considerations support a finding of non-obviousness of the ’954 claims. It contends that the experimental results described in the ’954 patent were unexpected. In support, Tyco cites the patent specification’s description of the inventor’s experimental results as “unexpected.” Unsupported statements in the specification, however, cannot support a finding of unexpected results.
Tyco next points to a 1985 letter sent by an FDA expert to the company employing the named inventor asking the company to “provide the rationale for the choice of the 7.5 mg dosage” in its experiment. The motivation for that request was not disclosed in the letter. That letter provides no indication that the FDA expert would have been surprised at the results disclosed in the ’954 patent.
Tyco also cites Dr. Orr’s declaration that, in light of the prior art already discussed, the results of the inventor’s experiment would have been surprising at the time. That statement is entitled to little weight in light of the lack of support in the record for Dr. Orr’s interpretation of the prior art. Tyco does not supply further evidence of unexpected results other than citations to the prior art previously discussed. On the evidence and argument in the summary judgment record, Tyco has not overcome Mutual’s clear and convincing showing of obviousness.
Finally, Tyco argues that the commercial success of Restoril® 7.5 mg capsules supports a finding of non-obviousness. It notes that over the past decade, annual sales of the capsules have averaged more than $30 million. The district court acknowledged the product’s commercial success but properly found that the evidence as a whole did not overcome Mutual’s strong prima facie case.
We therefore uphold the summary judgment determination of the district court that the two claims of the ’954 patent are invalid for obviousness.
Allen’s Observations: Yet another drug case where the active ingredient is known but only the specific dose within a disclosed range is new, and yet another obviousness finding by the CAFC. The rule is now clear. Without unexpected results or a clear teaching away, specific doses within a range (absent a claimed new effect) are difficult to patent—despite the other Graham factors and hind-sight expert declarations. Although this rule may decrease revenues for branded manufacturers, it will speed generics entering the market.
